Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma

<p>Abstract</p> <p>Background</p> <p>Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC).</p> <p>Methods</p> <p>An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluated <it>in vitro</it>. In addition, the <it>in vivo </it>effect of TS siRNA on tumor progression was assessed using a xenograft model.</p> <p>Results</p> <p>Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model.</p> <p>Conclusion</p> <p>TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.</p

Nocturnal enuresis—theoretic background and practical guidelines

Nocturnal polyuria, nocturnal detrusor overactivity and high arousal thresholds are central in the pathogenesis of enuresis. An underlying mechanism on the brainstem level is probably common to these mechanisms. Enuretic children have an increased risk for psychosocial comorbidity. The primary evaluation of the enuretic child is usually straightforward, with no radiology or invasive procedures required, and can be carried out by any adequately educated nurse or physician. The first-line treatment, once the few cases with underlying disorders, such as diabetes, kidney disease or urogenital malformations, have been ruled out, is the enuresis alarm, which has a definite curative potential but requires much work and motivation. For families not able to comply with the alarm, desmopressin should be the treatment of choice. In therapy-resistant cases, occult constipation needs to be ruled out, and then anticholinergic treatment—often combined with desmopressin—can be tried. In situations when all other treatments have failed, imipramine treatment is warranted, provided the cardiac risks are taken into account

Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell Functions

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On the use of parataxonomy in biodiversity monitoring: a case study on wild flora

International audienceMonitoring programs that assess species-richness and turnover are now regarded as essential to document biodiversity loss worldwide. Implementation of such programs is impeded by a general decrease in the number of skilled naturalists. Here we studied how morphotypes, instead of species, might be used by unskilled participants (referred to as “volunteers”) to survey common plant communities. Our main questions were: (1) Can morphotypes be used as a robust estimator of species-richness (alpha-diversity) and assemblage turnover (Beta-diversity)? and (2) What is the robustness (reproducibility and repeatability) of such methods? Double inventories were performed on 150 plots in arable Weld margins, one by a non-expert using morphotypes, the other by a taxonomist using species. To test the robustness of morphotype identiWcation among participants, 20 additional plots were surveyed by eight volunteers using the same protocol. We showed that (1) the number of morphotypes identiWed by unskilled volunteers in a plot was always strongly correlated with species-richness. (2) Morphotypes were sensitive to diVerences among habitats but were less accurate than species to detect these diVerences. (3) Morphotype identiWcation varied signiWcantly within and between volunteers. Due to this lack of repeatability and reproducibility, parataxonomy cannot be considered a good surrogate for taxonomy. Nevertheless, assuming that morphotypes are identiWed with standardized methods, and that results are used only to evaluate gross species-richness but not species turnover, parataxonomy might be a valuable tool for rapid biodiversity assessment of common wild flora

Clock genes and their genomic distributions in three species of salmonid fishes: Associations with genes regulating sexual maturation and cell cycling

<p>Abstract</p> <p>Background</p> <p>Clock family genes encode transcription factors that regulate clock-controlled genes and thus regulate many physiological mechanisms/processes in a circadian fashion. Clock1 duplicates and copies of Clock3 and NPAS2-like genes were partially characterized (genomic sequencing) and mapped using family-based indels/SNPs in rainbow trout (RT)(<it>Oncorhynchus mykiss</it>), Arctic charr (AC)(<it>Salvelinus alpinus</it>), and Atlantic salmon (AS)(<it>Salmo salar</it>) mapping panels.</p> <p>Results</p> <p>Clock1 duplicates mapped to linkage groups RT-8/-24, AC-16/-13 and AS-2/-18. Clock3/NPAS2-like genes mapped to RT-9/-20, AC-20/-43, and AS-5. Most of these linkage group regions containing the Clock gene duplicates were derived from the most recent 4R whole genome duplication event specific to the salmonids. These linkage groups contain quantitative trait loci (QTL) for life history and growth traits (i.e., reproduction and cell cycling). Comparative synteny analyses with other model teleost species reveal a high degree of conservation for genes in these chromosomal regions suggesting that functionally related or co-regulated genes are clustered in syntenic blocks. For example, anti-müllerian hormone (amh), regulating sexual maturation, and ornithine decarboxylase antizymes (oaz1 and oaz2), regulating cell cycling, are contained within these syntenic blocks.</p> <p>Conclusions</p> <p>Synteny analyses indicate that regions homologous to major life-history QTL regions in salmonids contain many candidate genes that are likely to influence reproduction and cell cycling. The order of these genes is highly conserved across the vertebrate species examined, and as such, these genes may make up a functional cluster of genes that are likely co-regulated. CLOCK, as a transcription factor, is found within this block and therefore has the potential to cis-regulate the processes influenced by these genes. Additionally, clock-controlled genes (CCGs) are located in other life-history QTL regions within salmonids suggesting that at least in part, trans-regulation of these QTL regions may also occur via Clock expression.</p

Effects of multidisciplinary teamwork on lead times and patient flow in the emergency department: A longitudinal interventional cohort study

BACKGROUND Long waiting times for emergency care are claimed to be caused by overcrowded emergency departments and non-effective working routines. Teamwork has been suggested as a promising solution to these issues. The aim of the present study was to investigate the effects of teamwork in a Swedish emergency department on lead times and patient flow. METHODS The study was set in an emergency department of a university hospital where teamwork, a multi-professional team responsible for the whole care process for a group of patients, was introduced. The study has a longitudinal non-randomized intervention study design. Data were collected for five two-week periods during a period of 1.5 years. The first part of the data collection used an ABAB design whereby standard procedure (A) was altered weekly with teamwork (B). Then, three follow-ups were conducted. At last follow-up, teamwork was permanently implemented. The outcome measures were: number of patients handled within teamwork time, time to physician, total visit time and number of patients handled within the 4-hour target. RESULTS A total of 1,838 patient visits were studied. The effect on lead times was only evident at the last follow-up. Findings showed that the number of patients handled within teamwork time was almost equal between the different study periods. At the last follow-up, the median time to physician was significantly decreased by 11 minutes (p = 0.0005) compared to the control phase and the total visit time was significantly shorter at last follow-up compared to control phase (p = <0.0001; 39 minutes shorter on average). Finally, the 4-hour target was met in 71% in the last follow-up compared to 59% in the control phase (p = 0.0005). CONCLUSIONS Teamwork seems to contribute to the quality improvement of emergency care in terms of small but significant decreases in lead times. However, although efficient work processes such as teamwork are necessary to ensure safe patient care, it is likely not sufficient for bringing about larger decreases in lead times or for meeting the 4-hour target in the emergency department.Åsa Muntlin Athlin, Ulrica von Thiele Schwarz and Nasim Farrohkni